Abstract
At some point early in the vertebrate lineage, two whole genome duplication events (1R, 2R) took place that allowed for the diversification and sub-/neo-functionalization of the glycoprotein hormones (GpHs). All jawed vertebrates possess the GpHs luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH), each of which are heterodimers with a common alpha subunit and unique beta subunits. In 2002, a novel glycoprotein hormone named thyrostimulin was described to have unique GpA2 and GpB5 subunits that were homologous to the vertebrate alpha and beta subunits. The presence of GpA2 and GpB5 in representative protostomes and deuterostomes indicates their ancestry in the GpH family. There are several reports of GpH subunit evolution, but none have included GpA2 and GpB5 for species in each major vertebrate class. Thus, we addressed the ancestry of two paralogous GpB5 subunits (GpB5a and GpB5b) that were previously only recognized in two teleost species. Our search for orthologous GpB5a and GpB5b sequences in representative vertebrates and phylogenetic analysis, in addition to the currently published evolutionary scenarios of the GpH family, supports that GpB5a and GpB5b are paralogs that arose from the first vertebrate whole genome duplication event (1R). Syntenic analysis supports lineage specific losses of GpB5a in chondrichthyes, basal actinopterygians, and tetrapods, and retention in coelacanth and teleosts. Additionally, we were unable to identify GpA2 transcripts from tilapia mRNA, suggesting that this species does not produce heterodimeric thyrostimulin. While the conserved or even species-specific functional role of thyrostimulin or its individual subunits are still unknown in vertebrates, the analyses presented here provide context for future studies on the functional divergence of the GpH family.
Highlights
In vertebrates, the glycoprotein hormone family includes luteinizing hormone (LH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), and chorionic gonadotropin (CG; in placental mammals only)
Our results confirm that teleosts possess two paralogous GpB5 subunits, GpB5a and GpB5b, which were likely products of 1R due to the presence and synteny of GpB5a in coelacanth and high support of the branching clades
Coelacanth GpB5a is a syntenic match to the teleosts, despite the phylogenetic analysis supporting its placement in the GpB5b clade
Summary
The glycoprotein hormone family includes luteinizing hormone (LH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), and chorionic gonadotropin (CG; in placental mammals only). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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